Rapid Escalation Research Articles

AN ANALYTICAL STUDY OF EXPOSURE AND VULNERABILITY IN INDIA – WITH REFERENCE TO WORLD RISK INDEX

The study delves into the intricate realm of disaster risk management through an in-depth exploration of the World Risk Index (WRI). The primary objectives of this research are to examine the diverse indicators utilized in the computation of the WRI, dissect the evolving trends encapsulated within the World Risk Report (WRR), and discern the factors catalyzing the rapid escalation of the risk factor index in the specific context of India. The research methodically dissects six pivotal factors contributing to the rapid increase in India's WRI, ranging from the profound impact of the COVID-19 virus to population dynamics, migration patterns, and the intricate interplay of overlapping disaster impacts. The redesign of the WRI model and miscellaneous factors, including challenges related to data availability, further enrich the analysis. As this study navigates the complexities of evaluating disaster risk, it aims to offer valuable insights into the multifaceted dimensions of risk. KEYWORDS: Disaster Management, World Risk Index, Exposure, Vulnerability, India

Evaluation of the protocol for rush subcutaneous immunotherapy with birch pollen extract

We previously reported the effectiveness of rush subcutaneous immunotherapy with birch pollen extract (Birch rSCIT) for pollen-food allergy syndrome (PFAS) and the high rate of systemic reactions (SR) during the rapid escalation phase. In this study, we examined whether modifying the dose escalation protocol of Birch rSCIT would reduce SR and maintain therapeutic effects. Birch rSCIT was introduced in 20 patients with PFAS who experienced systemic symptoms upon ingestion of soybeans. Birch rSCIT was implemented using 3 protocols: 2 protocols (nonstep-up group) increased the target dose to more than 1:2 × 102 (w/v) in 0.05 mL, while 1 protocol (step-up group) increased the target dose to 1:2 × 103 (w/v) in 0.3 mL, and then increased to 1:2 × 102 (w/v) in 0.05 mL using the conventional method in the following week. In the nonstep-up group, 4 out of 5 patients (80%), and in the step-up group, 2 out of 15 patients (13.3%) developed SR during rapid escalation. During the rapid escalation phase, the step-up group had significantly fewer SR than the nonstep-up group (P = 0.014). The median ingestible dose of soy milk in the oral food challenge was 3.5 mL before the treatment and increased significantly to 200 mL 1 year after initiating Birch SCIT (P < 0.01). We confirmed that reducing the target antigen dose in Birch rSCIT improved safety and maintained the therapeutic effect for soybean allergy with PFAS.

Multiple stimuli-responsive double perovskite structured Ca2MgWO6: x % Eu3+ (x = 1–11 mol) red-emitting luminescent systems to combat counterfeiting

The rapid escalation of counterfeiting activities in recent years has posed significant challenges across diverse fields, such as pharmaceuticals, currency, luxury goods, and electronics. In response, inorganic phosphors have emerged as promising tools to combat counterfeiting due to their inherent durability and stability. The present work focuses on the synthesis of Ca2MgWO6:x % Eu3+ (x = 1–11 mol) luminescent systems via a gel-combustion route. The structural analysis of the synthesized luminescent systems confirmed a monoclinic crystal phase with a P21/n space group. The morphological study of the luminescent system revealed a network-like structure comprising interconnected particles. Photoluminescence emission spectra show a prominent red emission peak at 616 nm, corresponding to the 5D0→7F2 4f–4f electronic transition of Eu3+ ions in the host matrix. The emitted red light demonstrates a color purity and quantum efficiency of 93.1 % and 77.41 %, respectively. The anti-counterfeiting security patterns were developed using the Ca2MgWO6:x % Eu3+ (x = 9 mol) luminescent system showcase virtually invisible under normal light. However, developed patterns exhibit vivid red luminescence when exposed to multiple stimuli UV light at 365 and 395 nm, which envisages the versatility of the systems for enhancing product authentication and protecting against fraudulent activities across multiple industries. The aforementioned results demonstrated the efficacy of Ca2MgWO6: Eu3+ luminescent systems for integration into advanced security measures.

Pediatric Early Warning Scores Before Rapid Response Poorly Predict Intensive Care Unit Transfers.

The Pediatric Early Warning Score (PEWS) is a clinical tool used to identify children at risk for clinical deterioration, but its utility remains debated, particularly in high-resource settings. Our objective with this study was to assess the predictive performance of the PEWS for unplanned PICU transfers after pediatric rapid response team (RRT) activation. A retrospective cohort study at a tertiary care academic children's hospital included all hospitalized patients up to 21 years old who had RRT activations between August 2021 and July 2022. Demographic and clinical data, the primary reason for RRT activation, and the modified Brighton PEWS were collected. The primary outcome was PICU transfer following RRT activation, and the secondary outcome was rapid escalation of care within 4 hours after RRT activation. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated at multiple PEWS thresholds. Of 297 RRT activations in 244 patients, 183 (63%) resulted in a PICU transfer, 75% of which were due to respiratory concerns. The PEWS was recorded in 89% of RRT activations within the preceding 4 hours. There was no significant difference in the PEWS between patients with or without PICU transfer or rapid escalation of care. The sensitivity, specificity, and AUROC of PEWS for predicting PICU transfer or rapid escalation of care were low (AUROC 0.495-0.613). PEWS within 4 hours before RRT activation was a poor predictor of PICU transfer or rapid escalation care. Further work is needed to develop a more sensitive and specific tool.

Untangling anti-Indian narratives in the 2019 Bolivian crisis: violence, anxiety and discourse

ABSTRACT The 2005 arrival of Evo Morales to power came with high expectations about the increased participation of indigenous people in the country’s social and political life. However, the violence perpetrated against urban indigenous people allied to MAS from the moment Morales stepped down has shone a light on the volatile nature of unresolved racial tensions in Bolivia. This article centers on the rapid escalation of anti-Indian racism during the 2019 electoral crisis and ensuing political conflict and the weight of anti-Indian racial narratives at the heart of the violence. Through an analysis of archives and data collected during the conflict through mediated approaches , this paper examines the 2019 crisis, focusing on the surge in anti-Indian violence, and briefly discusses pre-crisis anti-racist efforts by the MAS administration. Then, it reflects on the idea of the ‘savage Indian’ and racial regimes that produced key ‘discursive formations’ that continue to polarize Bolivia. It then critically assesses the ideology of mestizaje’s racial role in the crisis, positioning it within a broader anti-Indian narrative that confines Indianness to the past while hindering acknowledgement, reconciliation, and healing from racial trauma.

Research on the evolution law and control technology of deviatoric stress in the surrounding rock of gob-side entry retaining

Gob-side entry retaining (GER) play a crucial role in enhancing coal recovery, improving roadway stress conditions, and ensuring safe and efficient mining operations. This study focuses on investigating the stability characteristics of surrounding rock using flexible formwork concrete (FFC) along the headgate of 3405 panel. According to the fracture pattern of roof, a mechanical model of GER was developed. This study derived expressions for the support resistance of the filling body and determined its optimal bearing capacity. A FLAC3D numerical model was employed to simulate the GER process, segmented into early, middle, and late stages. Simulation results demonstrate a progression in peak deviatoric stress and extent of plastic zones in the surrounding rock. This evolution includes an initial minor increase (early stage), followed by rapid escalation (middle stage), and eventual stabilization (late stage). The middle stage emerges as critical, characterized by pronounced mining-induced stress effects on the roof. During this phase, significant changes are observed in deviatoric stress curves, with plastic zones rapidly migrating deeper into the rock mass. Practical implementation of the findings revealed a maximum deformation of the filling body of only 198 mm, affirming the feasibility of employing FFC in GER. This research provides valuable insights into managing stability concerns in GER thereby enhancing safety and operational efficiency in coal mining under similar conditions.

Internal damage evolution of C/SiC composites in air at 1650 °C studied by in-situ synchrotron X-ray imaging

Carbon fibre reinforced silicon carbide (C/SiC) ceramic matrix composites have attracted considerable attention due to their exceptional properties and extensive potential applications as high-temperature structural materials. However, due to their complex structure and manufacturing defects, C/SiC composites exhibit intricate mechanical behaviour under thermal-mechanical-oxidative coupling environments. To date, systematic studies on the internal damage evolution and failure mechanisms of C/SiC composites under high-temperature oxidative environments are lacking. In this study, a combination of synchrotron X-ray micro-computed tomography (SR-μCT) and in-situ experiments under thermal-mechanical-oxidative coupling environments at room temperature and 1650 °C in air was used to characterize the internal microstructures and damage evolution processes of C/SiC composites at different loading levels. Additionally, the 3D strain fields during in-situ loading were quantitatively analysed using the Digital Volume Correlation (DVC) method. The findings underscore the substantial impact of oxidative damage on the mechanical response of C/SiC composites, particularly concerning tensile properties and fracture modes. At room temperature, severe delamination, fibre bundle pull-out and interfacial debonding occurred internally. Whereas, under high-temperature atmospheric conditions, severe fibre oxidation reactions occurred at the specimen edges, resulting in rapid porosity escalation. Crack initiation from surface defects followed by rapid inward propagation is observed. Moreover, while the strain distribution remains relatively uniform until fracture, a pronounced concentration of strain is evident near the fracture zones at room temperature, with an even greater concentration observed at 1650 °C. Notably, the region of concentrated strain within the 3D deformation field corresponds closely to the final fracture location, as revealed by quantitative DVC analysis.

Dosing Strategies and Quantitative Clinical Pharmacology for Bispecific T-Cell Engagers Development in Oncology.

Bispecific T-cell Engagers (TCEs) are promising anti-cancer treatments that bind to both the CD3 receptors on T cells and an antigen on the surface of tumor cells, creating an immune synapse, leading to killing of malignant tumor cells. These novel therapies have unique development challenges, with specific safety risks of cytokine release syndrome. These on-target adverse events fortunately can be mitigated and deconvoluted from efficacy via innovative dosing strategies, making clinical pharmacology key in the development of these therapies. This review assesses dose selection and the role of quantitative clinical pharmacology in the development of the first eight approved TCEs. Model informed drug development (MIDD) strategies can be used at every stage to guide TCE development. Mechanistic modeling approaches allow for (1) efficacious yet safe first-in-human dose selection as compared with in vitro minimum anticipated biological effect level (MABEL) approach; (2) rapid escalation and reducing number of patients with subtherapeutic doses through model-based adaptive design; (3) virtual testing of different step-up dosing regimens that may not be feasible to be evaluated in the clinic; and (4) selection and justification of the optimal clinical step-up and full treatment doses. As the knowledge base around TCEs continues to grow, the relevance and utilization of MIDD strategies for supporting the development and dose optimization of these molecules are expected to advance, optimizing the benefit-risk profile for cancer patients.

Are 2D shallow-water solvers fast enough for early flood warning? A comparative assessment on the 2021 Ahr valley flood event

Abstract. Flash floods pose a distinct challenge compared to traditional fluvial flooding, with infrastructure-based solutions proving less effective. Effective responses hinge on advanced early warning systems providing actionable information, emphasising the necessity for computational flood forecasting models. However, hydrodynamic models, renowned for accuracy and completeness, face limitations due to computational intensity. This study explores two 2D flood forecasting models, RIM2D and SERGHEI, both with GPU implementations which allow us to maximise the forecast lead time. While RIM2D is less computationally intensive, suitable for operational use, SERGHEI, with higher computational costs, targets large-scale high-performance computing (HPC) systems. The assessment of applicability and trade-offs is carried out on the 2021 Eifel flood event, particularly in the lower Ahr valley. A set of simulations were performed at various resolutions from 1 to 10 m, which reveal similar accuracy among both models at coarser resolutions, yet discrepancies arise at finer resolutions due to the distinct formulations. Both models exhibit a rapid computational cost escalation, but at resolutions equal to or coarser than 5 m, forecasts are remarkably faster than the real-time ideal for operational use, paving the way for their use in early warning systems. However, higher resolutions necessitate multi-GPU and HPC capabilities, underlining the importance of embracing such technology in addressing broader flood domains.

Rational Design and Synthesis of CO2 Reduction Reaction Catalysts of High Faradaic Efficiency Toward C2 + Chemical Conversions

Carbon dioxide emission from fossil fuel combustion poses a major threat to global environment and ecological systems.Carbon capture, sequestration and conversion technologies are widely pursued as possible solutions to mitigate negative impact by CO2. The electrochemical CO2 reduction reaction (CO2RR) to fuels and chemicals using renewable electricity offers attractive “carbon-neutral” and “carbon-negative” mitigation strategies. Various catalysts have been investigated as the electrocatalysts for CO2RR. Key challenges facing the current catalyst and electrolyzer designs include insufficient energy efficiency and low single product selectivity.CO2RR to C2+ chemicals represent a highly important area for CO2 reduction and utilization. For example, ethanol, ethylene, propanol, etc. are among the most produced chemicals by the industry and are widely used for various applications. Using CO2 as raw material for chemical production through electrocatalysis not only improves the carbon cycling, but also reduces the overall emissions from chemical production. While CO2RR via two proton-electron pairs (PEPs), such as the conversion of CO2 to CO or formate, have been proven high selective with fast kinetics, conversions to C2+ chemicals are significantly more difficult due to the rapid escalation of required PEPs to much higher numbers (for example, 12 for ethanol and 18 for propanol), in addition to C-C bond coupling. The increased PEPs substantially complicate the conversion by required multiple steps along the electrochemical coordinate, leading to a high probability of branching reactions and low single product Faradaic efficiency (FE).To address these challenges, the design criteria for CO2RR to C2+ chemicals should be based on high uniformity of active center for directing identical catalytic path and suppressing competing reactions, strong catalyst-reactant binding in capturing the transient species through multiple PEP transfers, and microenvironment with nanoconfinement for retaining reaction intermediates during extended catalytic processes.Recently, we developed a new amalgamated lithium metal (ALM) synthesis method of preparing highly selective and active CO2RR catalyst and achieved > 90% FE for conversion of CO2 to ethanol [1]. Our have since expanded the approach to other C2 + chemicals including acetate, acetone, glycerol, isopropanol, etc., all with FE at or higher than 80%. To better formulate our catalyst design strategy, we not only measured the CO2RR performance over a variety of electrocatalysts, but also investigated their activity-structure relationship through advanced material characterizations, combined with the first-principle computation. We found many interesting properties uniquely associated to CO2RR mechanism and kinetics, such as catalyst-size and electro-potential modulated single selectivity. In this presentation, we will share our recent discoveries and future perspective on the development of highly selective CO2RR catalysts for C2+ chemical conversions. Acknowledgement: This work is supported by U. S. Department of Energy, Office of Energy Efficiency and Renewable Energy - Industrial Efficiency & Decarbonization Office and by Office of Science, U.S. Department of Energy under Contract DE-AC02-06CH11357.[1] “Highly selective electrocatalytic CO2 reduction to ethanol by metallic clusters dynamically formed from atomically dispersed copper” Haiping Xu, Dominic Rebollar, Haiying He, Lina Chong, Yuzi Liu, Cong Liu, Cheng-Jun Sun, Tao Li, John V. Muntean, Randall E. Winans, Di-Jia Liu and Tao Xu, (2020) Nature Energy, 5, 623–632

Detection of Bordetella spp. in children with pertussis-like illness from 2018 to 2024 in China

To evaluate the role of Bordetella pertussis (B. pertussis), B. parapertussis, B. holmesii, and B. bronchiseptica on pertussis resurgence in China, particularly the sharp rise since the latest winter. Nasopharyngeal swabs collected from children with pertussis-like illness from January 2018 to March 2024 were cultured to detect B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica, and tested for all of these except for B. bronchiseptica using a pooled real-time polymerase chain reaction (PCR) kit targeting insertion sequences ptxS1, IS481, IS1001, and hIS1001. Out of the collected 7732 nasopharyngeal swabs, 1531 cases tested positive for B. pertussis (19.8%, 1531/7732), and 10 cases were positive for B. parapertussis (0.1%, 10/7732). B. holmesii and B.bronchiseptica were not detected. The number of specimens and the detection rate of B. pertussis were 1709 and 26.9% (459/1709) in 2018, 1936 and 20.7% (400/1936) in 2019, which sharply declined to 308 and 11.4% (35/308) in 2020, 306 and 4.2% (13/306) in 2021, and then notably increased to 754 and 17.6% (133/754) in 2022, 1842 and 16.0% (295/1842) in 2023, 877 and 22.3% (196/877) in the first quarter of 2024. The proportion of children aged 3 to less than 6 years (preschool age) and 6 to 16 years (school age) in pertussis cases increased significantly during the study period, especially the proportion of school-aged children increased from 2.0% (9/459) in 2018 to 40.8% (80/196) in 2024. B. pertussis was the predominant pathogen among children with pertussis-like illness in China, with sporadic detection of B. parapertussis and no detection of B. holmesii or B.bronchiseptica. The preschool and school-age children are increasingly prevalent in B. pertussis infection cases, which may be associated with the latest rapid escalation of pertussis outbreak.

Fire-RPG: An Urban Fire Detection Network Providing Warnings in Advance

Urban fires are characterized by concealed ignition points and rapid escalation, making the traditional methods of detecting early stage fire accidents inefficient. Thus, we focused on the features of early stage fire accidents, such as faint flames and thin smoke, and established a dataset. We found that these features are mostly medium-sized and small-sized objects. We proposed a model based on YOLOv8s, Fire-RPG. Firstly, we introduced an extra very small object detection layer to enhance the detection performance for early fire features. Next, we optimized the model structure with the bottleneck in GhostV2Net, which reduced the computational time and the parameters. The Wise-IoUv3 loss function was utilized to decrease the harmful effects of low-quality data in the dataset. Finally, we integrated the low-cost yet high-performance RepVGG block and the CBAM attention mechanism to enhance learning capabilities. The RepVGG block enhances the extraction ability of the backbone and neck structures, while CBAM focuses the attention of the model on specific size objects. Our experiments showed that Fire-RPG achieved an mAP of 81.3%, an improvement of 2.2%. In addition, Fire-RPG maintained high detection performance across various fire scenarios. Therefore, our model can provide timely warnings and accurate detection services.

Entropy generation and heat transfer characteristics in MHD Casson fluid flow over a wedge with viscous dissipation and thermal radiation

AbstractThis investigation outlines the significance of MHD Falkner–Skan flow of non‐Newtonian fluid flow over a wedge. To study the non‐Newtonian flow, Casson fluid is taken. Additionally, this study explores heat and mass transport under the influence of viscous dissipation, Joule heating, and thermal radiation. This heat and mass transport investigation is carried out under the influence of thermal and concentration slip factors. Moreover, the entropy generation is also computed using the second law of thermodynamics. A set of nonlinear partial differential equations arises from the mathematical formulation of the problem. Similarity variables are then introduced to achieve a similarity solution. The leading differential equations are solved numerically using the Runge–Kutta‐4 method in conjunction with shooting techniques. Graphical representations are employed to demonstrate the physical significance of relevant parameters. The investigation presents and discusses the impact of various parameters on velocity, temperature, concentration and entropy profiles for three different positions of the wedge: stationary, forward‐moving, and backward‐moving. The main conclusions of the study are as follows: (1) Enhancing the magnetic parameter and wedge angle parameter leads to higher fluid velocity, (2) elevating both the Eckert and magnetic number results in a rapid escalation of fluid energy, (3) Skin friction coefficient increases gradually with an increase in the power law Falkner–Skan parameter.

European security and Finland’s policy during the Russian aggression against Ukraine

The purpose of this article is to analyze the influence of Finland on regional policy of NATO and the Russo-Ukrainian war. The article explores political, economic and military aspects of Finland and Ukraine in the light of the Russian aggression while considering their relationships and foreign policy goals on a regional level. The author draws attention to various aspects of Helsinki domestic and foreign policy that is directed to set a balance in the region and, at the same time, to support Kyiv militarily and economically in confrontation with Moscow. Finland’s active policy of promoting stability can be described as a two-track policy, whereby EU membership and intensified military cooperation with Western partners provide a basis for the maintenance and development of relations with Russia. The author focused on energy resources and its importance for Finland that has a long history of energy trade with Russia. The trade is practically one-directional, as Finland lacks domestic fossil fuel reserves in comparison with its substantial demand for energy, whereas Russia has significant export volumes. Along with the above-mentioned issues, the author is observing aggressive Russian military activities in the Baltic Sea region. Despite peaceful relationships with Finland, Moscow does not mind to remind neighboring countries who calls the tune in the region. Pursuing this purpose, Russia increases military activity in the Baltic Sea region with relatively frequent airspace and territorial water violations. As a result, there is a risk that collisions or provocations might lead to a rapid and uncontrolled escalation. So, Finland finds its important to keep open channels for political dialogue and to seek ways to re-activate existing confidence-building measures. Finland-NATO relationships are taken into consideration as well. The author described the process of Finland’s accession to the alliance. After almost 30 years of close partnership with NATO, Finland joined the Alliance on April 4, 2023. Its partnership with NATO was historically based on its policy of military non-alignment, which changed following Russia’s full-scale invasion of Ukraine in February 2022. Following Russia’s aggression, Ukraine has requested materiel assistance from the EU and NATO member countries. To date, Finland has donated 23 defence materiel packages to Ukraine. The combined value of all defence materiel packages submitted so far is now over EUR 2 billion.

Revealing the evolution of spatiotemporal patterns of urban expansion using mathematical modelling and emerging hotspot analysis

The rapid expansion of cities in developing countries has led to many environmental problems, and the mechanism of urban expansion (UE), as a more complex human-land coupled system, has always been a difficult issue to research. This paper introduces a new approach by establishing an analytical framework for spatiotemporal pattern mining, exemplified by studying the urban growth of Changsha City from 1990 to 2019. Initially, an emerging hotspot analysis model (EHA) is employed to examine the spatiotemporal changes of urban growth on a macro scale. Mathematical models are subsequently utilized to quantify the correlations between urban expansion and selected infrastructural and topographical factors. Building on these findings, the paper constructs mathematical models to further quantify the spatiotemporal evolution of various urban sprawl patterns across different regions, aiming to elucidate and quantify the significant variations in UE over time and space. The study reveals that, as an emerging city, Changsha's hotspots of urban expansion prior to 2003 were primarily concentrated in the city centre, subsequently spreading to the periphery. The radial influence of metro stations on UE is notably less than that of railway stations—approximately 3 km versus 8 km—and the impact diminishes rapidly before gradually tapering off. Moreover, UE in Changsha predominantly occurs on slopes with gradients ranging from 1.1° to 7.5°, and significant development capacity is observed at elevations between 36.1 m and 78.3 m above sea level, with a tendency for urban sprawl to migrate to lower elevations. The paper also identifies three distinct patterns of urban expansion across different regions: an initial slow-growth phase, followed by a rapid escalation to a peak, and subsequently a swift decline to near stagnation. Additionally, it highlights a significant correlation between the proportion of built-up areas at the micro-regional scale and the stages of UE. This correlation was quantitatively analysed by constructing a logistic function, which demonstrated a robust fit that effectively captures spatiotemporal heterogeneity in the dynamics of UE. These insights enhance the selection of drivers in urban simulation models and deepen the understanding of the complex dynamics that influence urban development.

Energy Dependence of the Low-frequency Quasiperiodic Oscillations in Swift J1727.8–1613

Based on observations from the Insight Hard X-ray Modulation Telescope (Insight-HXMT), an analysis of type C quasiperiodic oscillations (QPOs) observed during the outburst of the new black hole candidate Swift J1727.8–1613 in 2023 was conducted. This analysis scrutinized the QPO’s evolution throughout the outburst, particularly noting its rapid frequency escalation during two flare events. Utilizing the energy range covered by Insight-HXMT, a dependency of the QPO frequency on energy was observed. Below approximately 3 Hz, minimal variations in frequency with energy were noted, whereas clear variations with photon energy were observed when it exceeded approximately 3 Hz. Additionally, a sharp drop in the rate of change was observed when the frequency exceeded approximately 8 Hz. This behavior, similar to several previously reported sources, suggests the presence of a common underlying physical mechanism. Moreover, the QPO rms–frequency relationship can be explained by the Lense–Thirring precession model. The relationship between rms energy and phase lag with frequency suggests the black hole system as a high-inclination source.

China’s ‘Liquid’ Warfighting Shift and Its Implications for Possible Future Conflict

Some suggest that remote, precision strike warfare is a Western phenomenon motivated by aversion to high troop casualties among democratic leaders subject to re-election. Others contend that it is the result of a global transition in the way of modern war towards ‘liquid warfare’, centred around the disruption of adversary networks in the increasingly integrated and high-tech battlespace. This article advances the debate by applying the liquid warfare hypothesis to China’s post-1993 military reforms. It finds (a) that China’s development and embrace of its prevailing ‘systems destruction warfare’ concept constitutes a liquid shift in its warfighting approach, dispelling the contention that such transformations are necessarily linked with democratic political systems; and (b) that the liquidification of China’s warfighting approach has immediate implications for possible regional conflict scenarios, particularly those involving the United States, making them mutually costlier and susceptible to rapid escalation.

Survodutide, a promising agent with novel mechanism of action for treatment of obesity and type 2 diabetes

Activation of the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) may result in synergistic effects on glycemic control and weight reduction. Survodutide is a dual agonist of GLP-1R and GCGR under development for treatment of type 2 diabetes, obesity and non-alcoholic steatohepatitis (NASH). In a phase 2 trial of 16-week duration including patients with type 2 diabetes, subcutaneous survodutide given once weekly reduced glycated hemoglobin (HbA1c) levels by 1.5% versus placebo, which was comparable to the reduction achieved by semaglutide (1.0 mg/w). In another phase 2 trial of obese subjects without diabetes, percent weight loss with the highest dose of survodutide was 12.1% versus placebo and did not reach a plateau up to the end of follow-up at 46 weeks. Use of survodutide was associated with significant reduction in systolic and diastolic blood pressure and plasma triglycerides. The most common adverse effects of survodutide were gastrointestinal (GI) disorders reported by 55% of patients (versus 22% with placebo) in the diabetes trial and by 75% (versus 42% with placebo) in the obesity trial. Drug discontinuation rates were 16-25% with survodutide, 4% with semaglutide and 4-5% with placebo. Results of a phase 2 trial including patients with NASH are pending. The major limitation of survodutide is suboptimal tolerability due to GI adverse effects attributed in part to rapid dose escalation. Overall, survodutide is a promising candidate drug with a novel mechanism of action for treatment of type 2 diabetes and obesity. Phase 3 clinical trials, with slower dose titration of survodutide should clarify its efficacy and safety in a broader population of patients with type 2 diabetes, obesity and NASH.

Exploring the Health-Related Quality of Life and the Lived Experience of Adolescents Following Invasive Meningococcal Disease.

Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs. Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically. Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge. The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.

Effect of Abhyantara Snehapana and Vamana Karma in Patients with Normal and Abnormal to Lipid Profile

In the recent years, India and other developing countries are witnessing a rapid escalation in lifestyle disorders like diabetes, coronary artery disease, obesity, hypothyroidism, etc. The prime causative factor for all the lifestyle disorders is hyperlipidemia or dyslipidemia. Dyslipidemia is defined as a metabolic disorder that occurs due to abnormal blood lipid levels. This may lead to increase in the chances of atherosclerosis, heart attacks, stroke and other circulatory disorders. The abnormal lipid levels may include increase in triglycerides, VLDL, LDL and decrease in HDL. Vamana karma, a bio-purificatory emesis, being the major Panchakarma therapy has its greatest influence on almost all the lifestyle disorders. Lifestyle disorders aren’t possible without the involvement of Kapha dosha and Medho dhatu. Vamana is the first line of choice in the treatment of disorders caused by the aggravation of Kapha Dosha or Kapha associated with Pitta dosha. Vamana karma involves a pre-procedure called Snehapana, which include administration of high quantity of medicated lipids for a maximum period of seven days, followed by the bio-purificatory emesis or Vamana karma, a process of elimination of morbid Doshas from the oral route. Considering the high amounts of lipid usage in Snehapana, it becomes essential, to monitor its impact on lipid profile in patients undergoing Vamana karma for various etiologies. The present clinical study is of paramount importance as there were no previous studies on the impact of Sneha pana and Vamana in patients with both normal and abnormal lipid profiles. The statistical significance of results were quantitated by paired t test. Although Snehapana followed by Vamana, did not significantly alter levels of total cholesterol, and LDL, it did cause a significant reduction in triglycerides (p=0.0013) and VLDL (p=0.0038), improvement of HDL (P=0.02) in all the patients with abnormal lipid profile. However the values remained within the limit in patients with normal lipid parameters.